PROJECT SUMMARY/ABSTRACT ? Transgenic Mouse, ICSI and IVF Core The ability to introduce foreign genes or to selectively knock out endogenous genes in animals is of tremendous importance for basic and clinical research. In particular, with the advent of CRISPR/Cas technology, unprecedented opportunities for in vivo gene modulations have arisen. As such, transgenesis is a very powerful tool facilitating in vivo genome editing and transcription modulation, essential to dissect transcriptional, signaling, and environmental influences on the genetic basis of diseases but also for the development of novel therapeutic intervention strategies. Furthermore, mouse gamete manipulation, cloning technology, stem cell derivation, and -culture are a series of techniques that are essential for many successful research institutes in particular those with a focus on reproductive and developmental biology. During Phase I, the University of Hawaii Transgenic Mouse, ICSI and IVF Core (TMII) at the Institute for Biogenesis Research was established and made significant progress towards the goal of becoming independently supported within fifteen years, accumulated a large array of equipment for micromanipulation of mouse gametes and embryo culture and recruited experienced researchers to staff the Core laboratory. Funding during Phase II strengthened and developed the COBRE Center into a state-of-the-art facility with an outstanding track record in providing efficient and economic access to transgenic animals and related technologies, including CRISPR technologies. The services were provided to COBRE faculty, University of Hawaii researchers and scientists around the country. The Core continued the development of novel gene delivery technology, including making significant progress on targeted gene insertion. The objective of this Phase III COBRE application is to enhance and transform the Core into a self- sustained resource entity. Besides expanding our Core services, we will continue to work on improving the quality and delivery of these services and on enhancing and streamlining core operations. The Core will also enhance its outreach and focus on education and training as principal conduits for the acquisition of new customers at the University level. We will diversify our existing portfolio by coordinating and harmonizing our Core resources and services with those of the Molecular and Cellular Immunology (MCI) Core. We also aim to strengthen the core revenue base by increasing and diversify the contingent of investigators utilizing its many offerings. Specifically, we will expand our outreach, improve marketing activities and explore opportunities for collaborations with cores from other COBRE, INBRE and IDeA-CTR institutions.